Role of GATA-2 in bone marrow-derived mesenchymal stem cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 25860776
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Tohoku University
• Principal Investigator: Okitsu Yoko 東北大学, 大学病院, 助教 (80451558)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: GATA-2 / 間葉系幹細胞

Outline of Final Research Achievements

The bone marrow microenvironment comprises multiple cell niches derived from bone marrow mesenchymal stem cells (BM-MSCs). However, the molecular mechanism of BM-MSC differentiation is poorly understood. The transcription factor GATA2 is indispensable for hematopoietic stem cells (HSCs) function as well as other hematopoietic lineages, suggesting that it may maintain BM-MSCs in immature state and also contribute to their differentiation. To explore this possibility, we established BM-MSCs from human bone marrow. GATA2 loss- and gain-of-function analyses based on human BM-MSCs confirmed that decreased and increased GATA2 expression accelerated and suppressed BM-MSCs differentiation to adipocytes, respectively. When GATA2 knockdowned BM-MSCs were cocultured with CD34+ cells, HSC frequency and colony formation decreased, indicating that decreased GATA2 expression induced BM-MSC differentiation, particularly into adipocytes, leading to the decreased hematopoietic supporting capacity.

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